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Oliver W. Gramlich, Stephanie C. Joachim, Panagiotis Laspas, Philip F. Gottschling, Clemens Cuny, Norbert Pfeiffer, Franz H. Grus; Immune-driven Retinal Ganglion Cell Loss In MBP-induced Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2928.
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© ARVO (1962-2015); The Authors (2016-present)
Optic neuritis and experimental autoimmune encephalomyelitis (EAE) are mainly characterized by autoimmune inflammatory demyelination. Beside T-cell mediation, recently an involvement of antibodies has also been discussed. Aim of our study was to examine the effects of myelin basic protein (MBP) immunization on retinal ganglion cell (RGC) survival, optic nerve alteration, changes of antibody reactivity, and microglia.
Optic neuritis was induced in rats by immunization with MBP (MBP, n=10), pertussis toxin (PTX) and incomplete Freund’s adjuvant (IFA). A control group (CO, n=10) received only PTX and IFA in NaCl. EAE scoring, intraocular pressure (IOP) measurements, and funduscopies were performed regularly. Ganglion cell density was evaluated on cresyl stained retinal flatmounts after six weeks. Optic nerve demyelination was graded by 0-3 scoring (demyelination score=ds) after Luxol Fast Blue staining. IgG antibody deposition and activated microglia were investigated in retina and optic nerve sections via immunohistology. The intensity of autoreactive IgG antibodies was quantified in successive serum samples via tissue arrays. Data was analyzed using ANOVA, Tukey’s post hoc or t-test.
Significant RGC loss was detected in EAE animals six weeks after immunization (CO=3805 cells/mm2, MBP=3544 cells/mm2; p<0.05). Optic nerve demyelination was observed (MBP:ds=1.77, CO:ds=0.62; p<0.01) and IgG antibody deposits accumulated in the retina and axons of EAE animals. Activated microglia cells were significantly increased in retina of EAE animals (CO=2.15 cells/mm, MBP=6.15 cells/mm; p<0.05). A twofold higher amount of activated microglia was noticed in optic nerves of the MBP group (CO=3.16 cells/ROI, MBP=6.46 cells/ROI; p=0.03), while the number of ramified microglia was slightly decreased (CO=12.90, MBP=7.80; p=0.13). The level of IgG antibody reactivity against retina and optic nerve components continuously increased (p<0.05). We observed typical EAE progression but no changes in IOP (p=0.9) or abnormalities in fundi.
Immunization with MBP triggers antibody reactivity against ocular tissue and causes RGC loss and demyelination. This suggests that antibody reactivity and their deposition in retina and optic nerve are possibly involved in the induction of RGC apoptosis. Induced by this stimuli, microglia were activated and do also influence the ocular pathomechanisms in EAE optic neuropathy.
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